Hypofractionated Radiotherapy Efficacy for Post-Prostatectomy Patients - Asunción Hervás
October 14, 2024
Asunción Hervás disccusses the HYPORT-ES trial, which examines hypofractionated postoperative radiotherapy in prostate cancer. Dr. Hervás discusses the phase II trial's design, which evaluated the efficacy and toxicity of moderate hypofractionation (62.5 Gy in 25 fractions) for adjuvant and salvage radiotherapy. The study, involving 405 patients from 23 Spanish centers, shows low rates of acute and late gastrointestinal and genitourinary toxicity, with excellent biochemical control at three years (93%). Dr. Hervás compares these results favorably to conventional fractionation, noting potentially lower toxicity rates. They discuss the potential for moderate hypofractionation to become a standard of care in this setting, with Dr. Hervás recommending its use due to convenience, safety, and patient satisfaction. The conversation emphasizes the importance of advanced radiotherapy techniques and individual patient factors in treatment decisions, while highlighting the need for longer-term data to confirm chronic toxicity and efficacy outcomes.
Biographies:
Asunción Hervás, MD, PhD, Staff Physician, Department of Radiation Oncology, Ramón y Cajal Hospital, Madrid, Spain
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA
Biographies:
Asunción Hervás, MD, PhD, Staff Physician, Department of Radiation Oncology, Ramón y Cajal Hospital, Madrid, Spain
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA
Read the Full Video Transcript
Zachary Klaassen: Hi, my name is Zach Klaassen. I'm a urological oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm delighted to be joined today for an ESTRO 2024 discussion with Dr. Asunción Hervás, who is the Head of Brachytherapy and GU Tumor Unit at Ramón y Cajal Hospital, Madrid, Spain. Asunción, thanks so much for joining us today.
Asunción Hervás: Oh, thank you. Thank you very much, Dr. Klaassen. Hi, everyone. Thank you for your time. I'm going to present the results of the HYPORT-ES presented at the last ESTRO meeting.
HYPORT-ES is a Phase II trial of hypofractionated postoperative radiotherapy in prostate cancer. It's a collaborative prospective, one-arm, multicenter, Spanish Phase II trial, testing hypofractionated postoperative radiotherapy in prostate cancer.
The aim of this trial was to evaluate the efficacy and toxicity of moderate hypofractionation, 62.5 Gy in 25 fractions, in postoperative radiotherapy, ART and SRT radiotherapy. The primary endpoints were the incidence of treatment-related acute and late gastrointestinal and genitourinary adverse events. And the secondary endpoints were biochemical failure-free survival, disease-free survival, overall survival, and quality of life, with three different questionnaires.
Inclusion criteria included the presence of unfavorable pathological factors and biochemical failure. Prophylactic nodal irradiation was not allowed. And for the delineation of the volumes of interest, we used the Australian guidelines. And IMRT and IGRT were mandatory. And we permitted the use of androgen deprivation therapy. From July 2019 to July 2022, 405 patients were recruited from 23 Spanish centers.
And the results. The median age was 68. The Gleason score, the majority was Gleason seven, and 20% of this series was Gleason eight or higher. More than 50% of the patients were pT3 and positive margin. And the median of PSA pre-radiotherapy was 0.28. And 80% of this series received treatment as salvage radiotherapy. And nearly 50% of the patients used hormonal therapy. And the median of follow-up was 24 months.
In this graph, you can see the primary endpoints, the incidence of acute genitourinary and gastrointestinal toxicity. And you can see the levels of the toxicity Grade 2 or more were very low, seven Grade 2 and one Grade 3 for genitourinary, and gastrointestinal did not have any Grade 3 toxicity. And for chronic were higher, but not much higher than acute. And we had around 10% of Grade 2 and 2% Grade 3 chronic genitourinary, and gastrointestinal around 1% Grade 2 and Grade 3.
And the results on biochemical failure-free survival were 98%, 96%, and 93% for one, two, and three years, respectively. In summary, we can say hypofractionated postoperative radiotherapy in prostate cancer is a safe treatment with excellent acute and late genitourinary and gastrointestinal toxicity profile, and very good biochemical control. We need longer follow-up to confirm chronic toxicity, quality of life, and efficacy.
And I would like to take home these messages: moderate hypofractionation in the salvage setting and adjuvant is a safe treatment, with similar rates of toxicity, or even lower, and comparable oncologic outcomes. Individual patient factors and the possibility of advanced radiotherapy techniques should be considered when making treatment decisions. And I would like to ask you, with the accumulated evidence, RADICALS and NRG and these results, is moderate hypofractionation a standard of care in this clinical setting?
Thank you very much for your attention, and that's all. Thank you.
Zachary Klaassen: Dr. Hervás, thanks so much. Beautiful presentation and excellent data. Just looking at your primary results, looking at the acute and the chronic GU and GI toxicity, how did these compare to conventional fractionation in the salvage radiotherapy setting?
Asunción Hervás: Oh, yes. Globally, in the conventional fractionation for salvage and adjuvant radiotherapy, depending on the study, the series of the fractionation protocol used, acute Grade 2 or higher toxicity, genitourinary, can range from zero to 33%. For gastrointestinal acute toxicity, they range from about 40 to 70%. For late toxicities, around 11 to 33% for genitourinary, and for gastrointestinal, around zero to 30%. But with the new trials in moderate hypofractionation, for example, NRG, they report around 70% toxicity globally in the conventional fractionation, and 30% in the HYPORT arm. The RADICALS, they report Grade 3 or higher, one or 2% toxicity. And in our own trial, we had very low rates of toxicity Grade 2 or higher. And this data suggests that moderate hypofractionation is a promising approach with similar or lower toxicity levels with the same efficacy in the salvage and adjuvant radiotherapy. And definitely, the new technology is the key to these good results. Now we can design very precise and safe treatments.
Zachary Klaassen: Great answer. That's excellent. When you look at your biochemical failure-free survival, at about three years, about 93%, have you done any sort of subgroup or sensitivity analyses to look at maybe some of those characteristics that are giving worse outcomes? Or if you haven't run those analyses, in your opinion, are there certain patients that maybe aren't doing quite as well?
Asunción Hervás: Oh, yes. Yes, of course, we have analyzed it. But given the low number of events, we have not found any variables that had an impact on the results at this moment. But we have a series with more than 50% of patients with high-risk features. I'm sure that with longer follow-up, we will find a relationship between some baseline features and a worse outcome, I'm sure.
Zachary Klaassen: Absolutely. So I want to go back to your take-home message. I'll ask you the question. Do you think that moderate hypofractionation for salvage radiotherapy should be standard of care?
Asunción Hervás: Well, we know that moderate hypofractionation is the standard of care in the primary treatment of prostate cancer with radiotherapy. And evidence supporting its use in the salvage setting, adjuvant setting, is growing. And the results from recent trials suggest that moderate hypofractionation is a safe option, with similar rates of toxicity, or even lower, similar oncologic outcomes, particularly with modern radiation techniques.
In answer to your question, given the current data and my own experience, Spanish experience, I think that moderate hypofractionation could be recommended as a standard of care in the salvage and adjuvant radiotherapy setting. However, individual patient factors, and the possibility of advanced radiotherapy techniques should be considered when making treatment decisions, and additional long-term data is needed to consolidate its role in this area.
Zachary Klaassen: Wonderful. It's been a great discussion. I appreciate your time and expertise. Maybe just a couple of take-home messages for our patients to wrap up our discussion.
Asunción Hervás: Yes. Oh, I recommend to use the moderate hypofractionation, because it's more convenient for the institution and for the patients, and it's safe. And I think in my experience along the year, it's very well tolerated, and the patients are very happy with reducing the number of sessions. And I think in my department it is the standard of care. And for example, in primary treatment, we use SBRT as a standard of care, and 2.5 is a low dose per fraction. And I think yes, it's safe, and I recommend it. With new technology, yes, it's important. And with individual factors of the patients, with that selection of patients and very good technology, it's perfect. I recommend it.
Zachary Klaassen: Wonderful. Dr. Hervás, thanks so much for your time and expertise, and congratulations on this important clinical trial, and thanks for joining us on UroToday.
Asunción Hervás: Thank you. Thank you.
Zachary Klaassen: Hi, my name is Zach Klaassen. I'm a urological oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm delighted to be joined today for an ESTRO 2024 discussion with Dr. Asunción Hervás, who is the Head of Brachytherapy and GU Tumor Unit at Ramón y Cajal Hospital, Madrid, Spain. Asunción, thanks so much for joining us today.
Asunción Hervás: Oh, thank you. Thank you very much, Dr. Klaassen. Hi, everyone. Thank you for your time. I'm going to present the results of the HYPORT-ES presented at the last ESTRO meeting.
HYPORT-ES is a Phase II trial of hypofractionated postoperative radiotherapy in prostate cancer. It's a collaborative prospective, one-arm, multicenter, Spanish Phase II trial, testing hypofractionated postoperative radiotherapy in prostate cancer.
The aim of this trial was to evaluate the efficacy and toxicity of moderate hypofractionation, 62.5 Gy in 25 fractions, in postoperative radiotherapy, ART and SRT radiotherapy. The primary endpoints were the incidence of treatment-related acute and late gastrointestinal and genitourinary adverse events. And the secondary endpoints were biochemical failure-free survival, disease-free survival, overall survival, and quality of life, with three different questionnaires.
Inclusion criteria included the presence of unfavorable pathological factors and biochemical failure. Prophylactic nodal irradiation was not allowed. And for the delineation of the volumes of interest, we used the Australian guidelines. And IMRT and IGRT were mandatory. And we permitted the use of androgen deprivation therapy. From July 2019 to July 2022, 405 patients were recruited from 23 Spanish centers.
And the results. The median age was 68. The Gleason score, the majority was Gleason seven, and 20% of this series was Gleason eight or higher. More than 50% of the patients were pT3 and positive margin. And the median of PSA pre-radiotherapy was 0.28. And 80% of this series received treatment as salvage radiotherapy. And nearly 50% of the patients used hormonal therapy. And the median of follow-up was 24 months.
In this graph, you can see the primary endpoints, the incidence of acute genitourinary and gastrointestinal toxicity. And you can see the levels of the toxicity Grade 2 or more were very low, seven Grade 2 and one Grade 3 for genitourinary, and gastrointestinal did not have any Grade 3 toxicity. And for chronic were higher, but not much higher than acute. And we had around 10% of Grade 2 and 2% Grade 3 chronic genitourinary, and gastrointestinal around 1% Grade 2 and Grade 3.
And the results on biochemical failure-free survival were 98%, 96%, and 93% for one, two, and three years, respectively. In summary, we can say hypofractionated postoperative radiotherapy in prostate cancer is a safe treatment with excellent acute and late genitourinary and gastrointestinal toxicity profile, and very good biochemical control. We need longer follow-up to confirm chronic toxicity, quality of life, and efficacy.
And I would like to take home these messages: moderate hypofractionation in the salvage setting and adjuvant is a safe treatment, with similar rates of toxicity, or even lower, and comparable oncologic outcomes. Individual patient factors and the possibility of advanced radiotherapy techniques should be considered when making treatment decisions. And I would like to ask you, with the accumulated evidence, RADICALS and NRG and these results, is moderate hypofractionation a standard of care in this clinical setting?
Thank you very much for your attention, and that's all. Thank you.
Zachary Klaassen: Dr. Hervás, thanks so much. Beautiful presentation and excellent data. Just looking at your primary results, looking at the acute and the chronic GU and GI toxicity, how did these compare to conventional fractionation in the salvage radiotherapy setting?
Asunción Hervás: Oh, yes. Globally, in the conventional fractionation for salvage and adjuvant radiotherapy, depending on the study, the series of the fractionation protocol used, acute Grade 2 or higher toxicity, genitourinary, can range from zero to 33%. For gastrointestinal acute toxicity, they range from about 40 to 70%. For late toxicities, around 11 to 33% for genitourinary, and for gastrointestinal, around zero to 30%. But with the new trials in moderate hypofractionation, for example, NRG, they report around 70% toxicity globally in the conventional fractionation, and 30% in the HYPORT arm. The RADICALS, they report Grade 3 or higher, one or 2% toxicity. And in our own trial, we had very low rates of toxicity Grade 2 or higher. And this data suggests that moderate hypofractionation is a promising approach with similar or lower toxicity levels with the same efficacy in the salvage and adjuvant radiotherapy. And definitely, the new technology is the key to these good results. Now we can design very precise and safe treatments.
Zachary Klaassen: Great answer. That's excellent. When you look at your biochemical failure-free survival, at about three years, about 93%, have you done any sort of subgroup or sensitivity analyses to look at maybe some of those characteristics that are giving worse outcomes? Or if you haven't run those analyses, in your opinion, are there certain patients that maybe aren't doing quite as well?
Asunción Hervás: Oh, yes. Yes, of course, we have analyzed it. But given the low number of events, we have not found any variables that had an impact on the results at this moment. But we have a series with more than 50% of patients with high-risk features. I'm sure that with longer follow-up, we will find a relationship between some baseline features and a worse outcome, I'm sure.
Zachary Klaassen: Absolutely. So I want to go back to your take-home message. I'll ask you the question. Do you think that moderate hypofractionation for salvage radiotherapy should be standard of care?
Asunción Hervás: Well, we know that moderate hypofractionation is the standard of care in the primary treatment of prostate cancer with radiotherapy. And evidence supporting its use in the salvage setting, adjuvant setting, is growing. And the results from recent trials suggest that moderate hypofractionation is a safe option, with similar rates of toxicity, or even lower, similar oncologic outcomes, particularly with modern radiation techniques.
In answer to your question, given the current data and my own experience, Spanish experience, I think that moderate hypofractionation could be recommended as a standard of care in the salvage and adjuvant radiotherapy setting. However, individual patient factors, and the possibility of advanced radiotherapy techniques should be considered when making treatment decisions, and additional long-term data is needed to consolidate its role in this area.
Zachary Klaassen: Wonderful. It's been a great discussion. I appreciate your time and expertise. Maybe just a couple of take-home messages for our patients to wrap up our discussion.
Asunción Hervás: Yes. Oh, I recommend to use the moderate hypofractionation, because it's more convenient for the institution and for the patients, and it's safe. And I think in my experience along the year, it's very well tolerated, and the patients are very happy with reducing the number of sessions. And I think in my department it is the standard of care. And for example, in primary treatment, we use SBRT as a standard of care, and 2.5 is a low dose per fraction. And I think yes, it's safe, and I recommend it. With new technology, yes, it's important. And with individual factors of the patients, with that selection of patients and very good technology, it's perfect. I recommend it.
Zachary Klaassen: Wonderful. Dr. Hervás, thanks so much for your time and expertise, and congratulations on this important clinical trial, and thanks for joining us on UroToday.
Asunción Hervás: Thank you. Thank you.